, say investigators reporting the PROBASE study.
The study compared risk-adapted screening measures in men who had prostate-specific antigen (PSA) measured at age 45 with those who had PSA measurements plus DRE at age 50.
The results show that as a solitary screening tool, 99% of DREs did not raise suspicion for prostate cancer, and among the 57 cases where DRE did raise suspicion, only three men were found to have cancer, all of which were low-grade, reported Agne Krilaviciute, PhD, from the German Cancer Research Center in Heidelberg, and colleagues.
“We also see that the cancer detection rate by PSA is four times higher compared to the DRE detection. Around 18% of the tumors are located in the part of the prostate where DRE cannot detect them,” she said in an oral presentation at the European Association of Urology Congress.
The investigators found that the majority of prostate cancers that occurred in this relatively young population were International Society of Urological Pathology grade 1 (Gleason score 3 + 3 = 6) or grade 2 (Gleason 3 + 4 = 7). DRE yields positive results in only about 12% of cases of ISUP grade 1 or 2, they noted.
“We conclude that DRE as a solitary screening test does not lead to a significant PCa [prostate cancer] detection rate in young men,” Dr. Krilaviciute said.
Falling by the wayside
The study adds to the growing body of evidence that DRE may not be especially helpful as either a screening tool or when used in active surveillance of men with prostate cancer.
An international consensus panel found that DRE could be safely skipped for active surveillance when MRI and other more accurate and objective measures, such as biomarkers, are available.
A prostate cancer expert who was not involved in the PROBASE study told this news organization that when he was in medical school, it would have been considered a serious lapse of practice not to perform a DRE, but that things have changed considerably over the past several years.
“We have PSA now, we have technology with MRI, and the yield of digital rectal examination is very low,” commented Julio Pow-Sang, MD, chief of the genitourinary oncology program at Moffitt Cancer Center in Tampa, Fla.
“Empirically, it’s very rare to find positive cancer through rectal exam in this day and age of PSA,” he said, adding that the examination itself is highly subjective, with varying results depending on the skills of the particular examiner.
“I think that in time, with good studies like this, digital rectal exam specifically for prostate cancer is going to slowly fade away,” Dr. Pow-Sang said.
PROBASE was a randomized screening study enrolling men at age 45 to test a risk-adapted screening strategy using a baseline PSA value with the additional offer of DRE in a large subcohort of participants.
The study was conducted in Germany, and the authors note that the “German statutory early detection program recommends DRE as a stand-alone screening test starting annually at age 45.”
The PROBASE investigators enrolled 46,495 men from February 2014 through December 2019.
Among the first 23,194 men enrolled, 6,537 underwent DRE at enrollment without a study PSA test.
In this group, 6,480 DREs (99%) were not suspicious for cancer, and 57 (1%) were. Of those with suspected prostate cancer, 37 underwent biopsy and 20 did not. Of those biopsied, only two were found to have prostate cancer. This translated into a cancer detection rate of 0.03% for DRE.
After a median of 6.6 years of follow-up, only one additional case of ISUP grade 2 prostate cancer was detected among the 6,357 men who had DREs at enrollment, translating into a prostate cancer detection rate of .05%.
The investigators also looked at men who suspicious DRE findings at baseline. They assumed that a DRE-detectable tumor at age 45 would still be manifest 5 years later and should be detectable with PSA at age 50. Of the 57 men with initially suspicious findings, 11 returned for PSA screening but refused biopsy, and of this group only one had an elevated PSA level. He then underwent biopsy, but the findings were negative.
Of those who underwent biopsy on the basis of DRE, 16 had prostatitis, 14 had benign prostatic hyperplasia, 1 had high-grade prostatic intraepithelial neoplasia, 1 had atypical small acinar proliferation, and 3 had equivocal findings.
In total, the investigators found 24 tumors among men screened with DRE. Of these, 3 occurred in men with results deemed suspicious and 21 were in men with unsuspicious digital exams. All of the tumors were ISUP grade 1, 2, or 3 tumors.
Among 245 men who had biopsies for a PSA level equal to or higher than 3 ng/mL, primarily Prostate Imaging Reporting and Data System (PI-RADS) 3-5 tumors, DRE findings at the time of biopsy were unsuspicious in about 82% of cases, Dr. Krilaviciute said.
“We also used MRI data to determine what proportion of tumors would be potentially detectable by DRE. We estimated that around 18% of tumors are located in the upper part of the prostate, which is not detectable by DRE,” she said. “Even excluding those tumors, still the DRE detection rate is low in palpable tumors.”
Although DRE performed better in higher-grade tumors, 80% of the tumors in the PROBASE participants were ISUP grade 1 or 2 and were likely to be undetected by DRE, she added.
“In Germany, the recommendations for the screening still include 45-year-olds to go with annual DRE. The PROBASE trial allowed us to evaluate for the first time what was the diagnostic performance for DRE at such a young age, and we see that 99% of men undergoing DRE have no suspicious findings, and among the 1% of suspicious findings having cancers extremely unlikely,” she said.
The study was supported by Deutsche Krebshilfe (German Cancer Aid). Dr. Krilaviciute and Dr. Pow-Sang reported having no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.